Endocrine system mixture effects

Each subsystem may have various active sites for the toxic action of compounds. However, between subsystems, the same mixture is likely to cause quantitatively different responses. Because an organism is composed of an array of subsystems, the outcome of a mixture study with compounds with distinctly different modes of action on reproduction effects may demonstrate a response that is numerically similar to concentration addition, whereas the underlying responses in all subsystems (e.g., endocrine, energetic, and metabolic systems) may differ mechanistically. Although all this is theoretically plausible, the challenge still is to provide empirical evidence that the models derived accurately predict mixture effects in exposed species. 

Endocrine disruptor. An exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism or its progeny or (sub)popu-lations. 

Effects have also been observed on the environment. Rachel Carson s Silent Spring in the 1960s drew attention to effects on wildlife. Our Stolen Future (Colbom et al. 1996) created an interest in disruption of the endocrine system by chemicals, even in animals. Many cases of effects on natural animal populations can now be inferred from laboratory experiments, although confirmation in the environment is extremely difficult. For instance, organochlorinc concentrations in adult male bottlenose dolphins are approaching the levels associated with adverse effects found in marine mammals (Carballo et al. 2008), and exposures of tadpoles to a mixture of nine pesticides at environmentally occurring levels lead to developmental effects in most frogs, while none were observed when the pesticides were applied one at a time (Hayes et al. 2006). 

At times, such as in drug administration, lipophiles are deliberately added to hydrophilic pharmaceuticals to facilitate absorption. Most often, however, the administering of combinations of lipophilic and hydrophilic chemicals is unintentional and leads to enhanced toxic effects on the body. Once taken up by the body, the distribution, metabolism, immune system response, endocrine system response, and effects on a wide variety of organs in the body are impacted by the mixtures and their metabolites. 

Tobacco smoke is a complex mixture of more than 4000 different chemicals that has multiple toxic effects on the endocrine system. In... 

Toxic infertility as used here refers to adverse effects on the reproductive systems of human males and females that result from exposure to xenobiotic single chemicals and chemical mixtures. This infertility may be because of direct toxic effects on the male or female reproductive organs and endocrine systems, or on the developing fetus such that the fetus cannot be either conceived or carried to term after conception. Developmental toxicity, the onset of adverse effects on the developing fetus or child after birth are discussed in Chapter 24. 

One study that overcomes some of the shortcomings of those just cited reported adverse neurodevelopment outcomes following maternal exposures to 19 organic solvents and mixtures of these. 13 In this study, the women were occupationally exposed to the chemicals listed in Table 24.3. Also included in this table are the K, values and whether or not the specific chemical is a known teratogen or a known endocrine disruptor. 5 It is interesting to note that only three of the chemicals in the study—ethanol, trichloroethylene, and mineral spirits (a mixture of hydrocarbon solvents)—are endocrine disruptors. This shows that teratogenic effects can be induced by chemicals and mixtures that are independent of the endocrine system. 

All three conditions are manifest by immune, neurologic, and endocrine factors. 13,34 Numerous chemicals and chemical mixtures are known to affect the immune, CNS, and endocrine systems (Chapters 18, 22, and 25). Chemicals or chemical mixtures that are toxic to these three systems would be expected, at the very least, to exacerbate other causative effects, or to act alone as causative agents. 

A laboratory study on mice found that there was little or no observed effect when water containing nitrates (-4.39) alone, aldicarb (1.13) alone, or atrazine (2.61) alone at groundwater MCL levels were consumed. When consumed together, however, in drinking water at the MCLs for groundwater, the mixture altered immune, endocrine, and nervous system parameters. I26... 

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